Gut Microbiota Alterations and Primary Glomerulonephritis in Children: A Review (original) (raw)

Intestinal microbiota in pediatric patients with end stage renal disease: a Midwest Pediatric Nephrology Consortium study

Microbiome, 2016

End-stage renal disease (ESRD) is associated with uremia and increased systemic inflammation. Alteration of the intestinal microbiota may facilitate translocation of endotoxins into the systemic circulation leading to inflammation. We hypothesized that children with ESRD have an altered intestinal microbiota and increased serum levels of bacterially derived uremic toxins. Four groups of subjects were recruited: peritoneal dialysis (PD), hemodialysis (HD), post-kidney transplant and healthy controls. Stool bacterial composition was assessed by pyrosequencing analysis of 16S rRNA genes. Serum levels of C-reactive protein (CRP), D-lactate, p-cresyl sulfate and indoxyl sulfate were measured. Compared to controls, the relative abundance of Firmicutes (P = 0.0228) and Actinobacteria (P = 0.0040) was decreased in PD patients. The relative abundance of Bacteroidetes was increased in HD patients (P = 0.0462). Compared to HD patients the relative abundance of Proteobacteria (P = 0.0233) was i...

Clinical Significance of Probiotics for Children with Idiopathic Nephrotic Syndrome

Nutrients, 2021

We previously reported that a decrease in butyrate-producing bacteria in the gut is a potential cause of regulatory T cell (Treg) abnormalities in children with idiopathic nephrotic syndrome (INS). Therefore, we hypothesized that administration of butyrate-producing bacteria might reduce INS relapse and the need for immunosuppressants in these patients. Twenty patients in remission from INS (median age 5.3 years, 15 boys) were enrolled in the study and assigned to receive either daily oral treatment with a preparation of 3 g Clostridium butyricum or no probiotic treatment. The number of relapses and requirement for immunosuppressive agents were compared between the two groups. In the probiotic treatment group, analyses of the gut microbiota and Treg measurements were also performed. Probiotic-treated patients experienced fewer INS relapses per year compared with non-probiotic-treated patients (p = 0.016). Further, administration of rituximab in the probiotic treatment group was sign...

Modulation of the microbiota by oral antibiotics treats immunoglobulin A nephropathy in humanized mice

Nephrology Dialysis Transplantation

Background Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. IgA is mainly produced by the gut-associated lymphoid tissue (GALT). Both experimental and clinical data suggest a role of the gut microbiota in this disease. We aimed to determine if an intervention targeting the gut microbiota could impact the development of disease in a humanized mouse model of IgAN, the α1KI-CD89Tg mice. Methods Four- and 12-week old mice were divided into two groups to receive either antibiotics or vehicle control. Faecal bacterial load and proteinuria were quantified both at the beginning and at the end of the experiment, when blood, kidneys and intestinal tissue were collected. Serum mouse immunoglobulin G (mIgG) and human immunoglobulin A1 (hIgA1)-containing complexes were quantified. Renal and intestinal tissue were analysed by optical microscopy after haematoxylin and eosin colouration and immunohistochemistry with anti-hIgA and anti-mouse CD11b antibodi...

Gut microbiota in Immunoglobulin A Nephropathy: a Malaysian Perspective

BMC Nephrology

Introduction The alteration of the gut microbiome in the gut-kidney axis has been associated with a pro-inflammatory state and chronic kidney disease (CKD). A small-scaled Italian study has shown an association between the gut microbiome and Immunoglobulin A Nephropathy (IgAN). However, there is no data on gut microbiota in IgAN in the Asian population. This study compares the gut microbial abundance and diversity between healthy volunteers and Malaysian IgAN cohort. Methods A comparative cross-sectional study was conducted involving biopsy-proven IgAN patients in clinical remission with matched controls in a Malaysian tertiary centre. Demographic data, routine blood and urine results were recorded. Stool samples were collected and their DNA was extracted by 16S rRNA gene sequencing to profile their gut microbiota. Results Thirty-six IgAN patients (13 male; 23 female) with the mean age of 45.5 ± 13.4 years and median estimated glomerular filtration rate (eGFR) of 79.0 (62.1–92.2) ml...

The Gut and Blood Microbiome in IgA Nephropathy and Healthy Controls

Kidney360

Background: IgA nephropathy (IgAN) has been associated with gut dysbiosis, intestinal membrane disruption and translocation of bacteria into blood. Our study aimed to understand the association of gut and blood microbiomes in IgAN patients in relation to healthy controls. Methods: We conducted a case control study with 20 progressive IgAN patients matched with 20 healthy controls, analyzing bacterial DNA quantitatively in blood by 16S PCR and qualitatively in blood and stool by 16S metagenomic sequencing. Between group comparisons as well as comparisons between the blood and gut microbiomes were conducted. Results: Higher median 16S bacterial DNA in blood was found in the IgAN group compared to the healthy controls group (7410 vs 6030 16SrDNA copies/uL blood, p = 0.04). Alpha and beta diversity in both blood and stool was largely similar between the IgAN and healthy groups.. Higher proportions of class Coriobacteriia, and species of genera legionella, Enhydrobacter and parabacteroid...

Fecal Microbiota Transplantation Modulates Renal Phenotype in the Humanized Mouse Model of IgA Nephropathy

Frontiers in Immunology, 2021

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis. Several observations suggest that gut microbiota could be implicated in IgAN pathophysiology. Aiming at exploring whether microbiota modulation is able to influence disease outcome, we performed fecal microbiota transplantation (FMT) from healthy controls (HC-sbjs), non-progressor (NP-pts) and progressor (P-pts) IgAN patients to antibiotic-treated humanized IgAN mice (α1KI-CD89Tg), by oral gavage. FMT was able to modulate renal phenotype and inflammation. On one hand, the microbiota from P-pts was able to induce an increase of serum BAFF and galactose deficient-IgA1 levels and a decrease of CD89 cell surface expression on blood CD11b+ cells which was associated with soluble CD89 and IgA1 mesangial deposits. On the other hand, the microbiota from HC-sbjs was able to induce a reduction of albuminuria immediately after gavage, an increased cell surface expression of CD89 on blood CD11b+ cells and a decre...

Microbiome, Immunosenescence, and Chronic Kidney Disease

Frontiers in Medicine, 2021

The gut microbiome is known as an important predictive tool for perceiving characteristic shifts in disease states. Multiple renal diseases and pathologies seem to be associated with gut dysbiosis which directly affects host homeostasis. The gastrointestinal-kidney dialogue confers interesting information about the pathogenesis of multiple kidney diseases. Moreover, aging is followed by specific shifts in the human microbiome, and gradual elimination of physiological functions predisposes the microbiome to inflammaging, sarcopenia, and disease. Aging is characterized by a microbiota with an abundance of disease-associated pathobionts. Multiple factors such as the immune system, environment, medication, diet, and genetic endowment are involved in determining the age of the microbiome in health and disease. Our present review promotes recently acquired knowledge and is expected to inspire researchers to advance studies and investigations on the involved pathways of the gut microbiota ...

Gut Microbiota in Chronic Kidney Disease: A Narrative Literature Review

Bioscientia medicina, 2024

Chronic kidney disease (CKD) is a growing public health problem related to loss of kidney function and cardiovascular disease as the main causes of morbidity and mortality in CKD. It is known that CKD is associated with intestinal dysbiosis. There is an influence of the gut microbiota on the gutkidney axis and it works reciprocally: on the one hand, CKD significantly changes the composition and function of the gut microbiota. On the other hand, gut microbiota is able to manipulate the processes that cause the emergence and progression of CKD through inflammatory, endocrine and neurological pathways. Understanding the complex interactions between gut and kidney microbiota may provide novel nephroprotective interventions to prevent the progression of CKD by therapeutically targeting balance of gut microbiota composition.

Microbiota and Metabolome Associated with Immunoglobulin A Nephropathy (IgAN)

PLoS ONE, 2014

This study aimed at investigating the fecal microbiota, and the fecal and urinary metabolome of non progressor (NP) and progressor (P) patients with immunoglobulin A nephropathy (IgAN). Three groups of volunteers were included in the study: (i) sixteen IgAN NP patients; (ii) sixteen IgAN P patients; and (iii) sixteen healthy control (HC) subjects, without known diseases. Selective media were used to determine the main cultivable bacterial groups. Bacterial tag-encoded FLX-titanium amplicon pyrosequencing of the 16S rDNA and 16S rRNA was carried out to determine total and metabolically active bacteria, respectively. Biochrom 30 series amino acid analyzer and gas-chromatography mass spectrometry/solid-phase microextraction (GC-MS/SPME) analyses were mainly carried out for metabolomic analyses. As estimated by rarefaction, Chao and Shannon diversity index, the lowest microbial diversity was found in P patients. Firmicutes increased in the fecal samples of NP and, especially, P patients due to the higher percentages of some genera/species of Ruminococcaceae, Lachnospiraceae, Eubacteriaceae and Streptococcaeae. With a few exceptions, species of Clostridium, Enterococcus and Lactobacillus genera were found at the highest levels in HC. Bacteroidaceae, Porphyromonadaceae, Prevotellaceae and Rikenellaceae families differed among NP, P and HC subjects. Sutterellaceae and Enterobacteriaceae species were almost the highest in the fecal samples of NP and/or P patients. Compared to HC subjects, Bifidobacterium species decreased in the fecal samples of NP and P. As shown by multivariate statistical analyses, the levels of metabolites (free amino acids and organic volatile compounds) from fecal and urinary samples markedly differentiated NP and, especially, P patients.